Morphine concentrations

Calibration graph (d) may be used to correct for the small fluorescence intensity due to morphine in NaOH this is not negligible when the morphine concentration is high and the codeine concentration is low. 

Conversion from Avinza to other pain control therapies - It is important to remember that the persistence of Av/> za-derived plasma morphine concentrations may be in excess of 36 hours when making a conversion to other pain control therapies. 

Figure 15.9 Competitive morphine sensor response as a function of the morphine concentration (0-10 p-g/mL) present in the solution. Three sensor types were examined morphine molecular imprinted polymer (M-MIP), reference (O-MIP), and agarose-covered platinum electrode (Pt-Ag). Reprinted from Kriz and Mosbach (1995). Copyright 1995 Elsevier Science.

Klepstad, P., S. Kaasa, and P.C. Borchgrevink, Start of oral morphine to cancer patients effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine, Eur. J. Clin. Pharmacol., 55(10), 713-719, 2000. 

An alkaloid pain reliever, morphine, is an often abused drug. Chronoampero-metric MIP chemosensors have been devised for its determination [204]. In these chemosensors, a poly(3,4-ethylenedioxythiophene) (PEDOT) film was deposited by electropolymerization in ACN onto an ITO electrode in the presence of the morphine template to serve as the sensing element [204], Electrocatalytic current of morphine oxidation has been measured at 0.75 V vs AglAgCllKClsat (pH = 5.0) as the detection signal. A linear dependence of the measured steady-state current on the morphine concentration extended over the range of 0.1-1 mM with LOD for morphine of 0.2 mM. The chemosensor successfully discriminated morphine and its codeine analogue. Furthermore, a microfluidic MIP system combined with the chronoamperometric transduction has been devised for the determination of morphine [182] with appreciable LOD for morphine of 0.01 mM at a flow rate of 92.3 pL min-1 (Table 6). 

Moreover, 0.5-pm diameter MIP beads have been prepared for chronoamperometric determination of morphine [204]. These beads were synthesized by thermo-radical precipitation polymerization of the MAA functional monomer, TRIM cross-linker, AIBN initiator and morphine template in the ACN solution. Then the beads were immobilized in a film of the PEDOT conducting polymer, electropolymerized onto the ITO electrode. The morphine detection with the use of the resulting chemosensor was much more sensitive to morphine (41.63 pA cm 2 mM for the morphine concentration range of 0.1-2 mM) than to morphine analogues. LOD for morphine was 0.3 mM. 

The concentrations of morphine and codeine in both raw opium and poppy straw vary greatly, but morphine concentrations as a percentage of total weight are typically about 10 times greater than are those of codeine. Therefore, processing of opium and poppy straw produces much more morphine than codeine. However, greater quantities of codeine than morphine are required for medical purposes. Based on the discrepancies between production and use of the two drugs, about 80% of morphine is converted into codeine. 

In a review of 239 cases of heroin-related drug deaths between 1997 and 2000, 18 deaths were associated with non-intravenous administration (49). The median morphine concentration in these non-injectors was 0.05 mg/g and this was significantly lower than in injectors (2.3 mg/ g). There was concurrent use of alcohol, other illicit drugs, and/or pharmaceutical formulations in 17 of the 18 cases. 

A 43-year-old man was found dead in bed after injecting metamfetamine and morphine the night before. An autopsy showed mild edema of the brain and lungs, fatty liver, and active HCV hepatitis. The postmortem findings suggested hyperthermia. The blood metamfetamine concentration was 550 ng/ml, and the blood morphine concentration was 760 ng/ml. 

In both cases, the blood metamfetamine concentration was less than the lethal concentration of 4.5 pg/ml. Morphine concentrations were higher than the non-toxic concentration of 0.3 pg/ml. It is unlikely that morphine was the cause of death, because it would have caused hypothermia instead of hyperthermia. It is more likely that morphine interacted with metamfetamine, increasing the hyperthermic effect that is typical of metamfetamine overdose. This would explain why hyperthermia caused death, despite a non-lethal blood concentration of metamfetamine. 

Nakahara et al. studied the disposition of 6-AM in monkey and human hair. 6-AM and morphine were present in all hair samples, and heroin was not detected. In addition, the concentration of 6-AM was greater than the concentration of morphine. Nakahara et al. also evaluated the total morphine content (heroin and 6-AM were hydrolyzed to morphine) in monkey hair following subcutaneous administration of heroin (2.5 mg) and morphine (10 mg). Although the morphine dose was 4 times greater than the heroin dose, the mean morphine concentration was only about two thirds of that found following heroin administration. The results indicate that heroin and 6-AM are incorporated more readily into hair than morphine. Based upon this information, the theoretical distribution of heroin and its metabolites in hair is illustrated in Figure 6. 

Criteria for the differentiation of heroin use from other forms of opioid exposure based upon hair analysis have been proposed by Moeller et al. Data from over 1000 hair analyses were evaluated, and the following criteria must be met in order to establish heroin use if the morphine concentration <1.0ng/mg, the morphine-to-codeine ratio must be >5 1 if the morphine concentration >1.0 ng/mg, the morphine-to-codeine ratio must be >2 1. In addition, the presence of 6-AM is definitive evidence of heroin exposure, since it can only be derived from metabolism of heroin. 

Sachs, H., Schmidl, D., Hages, G., and Schwilk, B., Morphine concentration in hair after consumption of poppy seed and oral administration of MST, Int. ]. Leg. Med., in press. 

Coombs DW, Fratkin JD, Meier FA, Nierenberg DW, Saunders RL. Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study. Pain 1985 22(4) 337-51. 

An unbound morphine blood concentration of 100 ngl ml or more is considered potentially fatal. However, fatal cases of heroin intoxication occur in patients with blood morphine concentrations below 100 ng/ml. In 62 cases of heroin intoxication, death was associated with unbound morphine heart blood concentrations below 100 ng/ml in 21 cases and 100 ng/ml or over in 41 cases (51). In the 21 with low concentrations, respiratory tract infections occurred more often, and plausible causes of death were identified in 19. 

Koch A, Reiter A, Meissner C, Oehmichen M. Ursache des Todes von Heroinkonsnmenten mit niedrigen Morphin-Konzentrationen im Bint. [Canse of death in heroin users with low blood morphine concentration.] Arch Kriminol 2002 209(3-4) 76-87. 

Dihydromorphine undergoes the same oxidative dimerization as morphine, but a mixture of both alkaloids yields a mixed dimer. The three possible dimers were separated by HPLC and from the relative peak areas the morphine concentration could be determined. The retention time of a series of dimers is given in Table 7.12. For a large number of drugs it was reported that no interference was observed when this method was used. The absolute sensitivity determined by the detection limit of the fluorimeter was 4 ng. 

Opiate effects on Ca + fluxes have been shown in a number of different experimental preparations. Kakunaga (57) reported that a high concentration of morphine (10 M) inhibited K+ and EDTA stimulated Ca + influx and efflux in rat brain slices. The effect was partially nalorphine reversible, was seen in low-Ca + medium (0.1 mM), but not at a higher Ca + concentration (1.3 mM). We have re-examined these phenomena and have found naloxone-reversible morphine inhibition of K+-stimulated Ca + uptake into brain slices from cortex or midbrain, but not cerebellum (10). Unlike the earlier report this effect was observed at Ca + concentrations up to 1.4 mM. These results were not obtained below morphine concentrations... 

Rats, which suffer from arthritis have an elevated morphine concentration in their spinal cord and urine. It is presumed, that also the human body produces endogenous morphine for pain regulation during the course of particular illnesses. 

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